Abstract :
The renin-angiotensin system (RAS) is one of the oldest known hormone systems. Its effector hormone, angiotensin (Ang) II, acts through 2 receptor subtypes, AT1 and AT2. Most physiologic effects of Ang II, including vasoconstriction, renal salt and water retention, aldosterone and vasopressin release, and sympathetic facilitation, are mediated by AT1. Recent data, however, suggest that Ang II also contributes to cell proliferation, left ventricular hypertrophy, vascular media hypertrophy, neointima formation in atherosclerosis, and nephrosclerosis by stimulation of AT1 receptors. AT2 receptors are associated with antiproliferation, cell differentiation and development, tissue regeneration, and apoptosis. They also antagonize AT1 receptor–mediated effects, which suggests that the ratio of angiotensin receptors expressed on a particular cell can determine the net effect of Ang II. Selective AT1 receptor antagonists (″sartans”) have been used to treat several million hypertensive patients worldwide. These agents offer a powerful therapeutic alternative to angiotensin-converting enzyme (ACE) inhibitors, which reduce the generation of Ang II. Conversely, AT1 receptor antagonists block the RAS by acting on cellular angiotensin receptors and do not interfere with the breakdown of kinins. These medications inhibit the RAS more completely than do the ACE inhibitors because their action is independent of Ang II–generating pathways. At the same time, early, preliminary data suggest that AT1 receptor antagonists offer target-organ protection similar to that provided by the ACE inhibitors. Because AT2 receptors are left unopposed and Ang II levels are increased with AT1 receptor antagonist treatment, it is important to understand the function of AT2 to fully appreciate the mechanisms of action of AT1 receptor antagonists, especially their potential for target-organ protection. (Am Heart J 2000;139:S2-S8.)
